Sulthiame induced carbonic anhydrase inhibition is associated with improvement of nocturnal oxygenation in OSA patients

Abstract

Introduction and background

We recently demonstrated that sulthiame (STM), a carbonic anhydrase (CA) inhibitor, reduced the apnea-hypopnea index (AHI) in patients with obstructive sleep apnea (OSA) (Hedner et al. AJRCCM 2022). Evaluation of CA activity during CA inhibition has not been evaluated as a biomarker in OSA.

Aims and objectives: An independent analysis of biobank samples generated from the double-blind, placebo-controlled trial was performed to explore the effects of STM on blood CA activity and the association between blood CA activity and metrics of hypoxia during sleep in patients with OSA.

Methods: Patients with moderate-to-severe OSA (70% male, age 61±10 years, body mass index 28±3 kg/m² and AHI 56±23 events/h) were randomized to receive STM 200 mg (n=9), STM 400 mg (n=23) or placebo (n=18) for 4 weeks. Hemoglobin-adjusted blood CA activity was analyzed by a CA activity assay kit (Biovision, Cat#K473) at baseline and at the end of trial. Sleep related variables were derived from conventional polysomnography.

Results: Baseline AHI and CA activity did not differ between groups. STM 400 mg reduced blood CA activity by 24 % (p<0.001 vs. baseline). Corresponding changes for STM 200 mg and placebo were -6 % and +5 % (both p>0.1). Suppression of CA by STM 400 mg was associated with increased overnight mean and minimum SpO₂ (r=0.43 and 0.44, p=0.048 and 0.039, respectively) as well as with AHI reduction (r=-0.38, p=0.081).

Conclusions: STM-reduced CA activity was correlated with improved nocturnal oxygenation. CA activity may be a useful biomarker to further explore the underlying mechanisms of STM treatment in OSA. (AMK/SM contributed equally)